Eclectic enzymes: Easily modified building blocks for drug design

Sep 02, 2010
Eclectic enzymes: Easily modified building blocks for drug design

(PhysOrg.com) -- In the pursuit of biologically active compounds, it is often necessary to be able to control the stereochemistry at predefined positions in a molecular skeleton. The search for ways to prepare chiral building blocks with known configuration that also show structural differentiation is important.

Italian scientists working with Elisabetta Brenna have developed a technique to separate individual stereoisomers of building blocks that can be easily integrated into biologically active molecules. As the scientists from Politecnico di Milano, Milano, Italy, report in the , their technique relies on the use of enzymes.

The specific activity of a biologically relevant molecule is often dependent on its stereochemistry (i.e., the spatial arrangement of its atoms). However, most compounds showing have complex structures, making their synthesis difficult. Moreover, compounds with differing stereochemistries can show different activities. Thus, it is sometimes desirable to prepare a range of compounds with the same structural backbone, but having different spatial arrangements of their atoms. The use of configurationally defined building blocks is attractive, but a method to obtain all the stereoisomers of a given building block is thus required.

Brenna and her colleagues have developed a method that allows a mixture of isomers to be differentiated, and it depends on the use of the enzyme lipase PS. The resolution of the stereoisomers relies on the preferential reaction of the enzyme with only one , thereby creating a product mixture containing the desired compound and a mixture of the unreacted isomers. The desired product can be easily separated from the unreacted mixture, which can then be resubjected to the enzyme to undergo further . In this way, a wide range of building blocks with differing and known stereochemistries can be prepared.

The authors then showed the applicability of their method by incorporating their configurationally defined building blocks into biologically active compounds. Using simple and straightforward organic chemistry transformations, the authors were able to embed their building blocks into two classes of compounds that are of biological interest. Importantly, scientists can now easily examine the biological activities of all the different stereoisomers of a given compound. Thus, the Italian team is well on their way to helping scientists screen a diverse range of potential drugs that may lead to the treatment, cure, prevention, or diagnosis of diseases.

Explore further: Chemical biologists find new halogenation enzyme

More information: Elisabetta Brenna, et al., Oxygenated Stereotriads with Definite Absolute Configuration by Lipase-Mediated Kinetic Resolution: De Novo Synthesis of Imino Sugars and 6-Deoxy-C-glycosides, European Journal of Organic Chemistry, 2010, No. 23, 4468-4475, dx.doi.org/10.1002/ejoc.201000558

Related Stories

Building blocks of the future

Apr 06, 2010

(PhysOrg.com) -- Professor Varinder Aggarwal is no ordinary builder. He and his team in the School of Chemistry have just discovered a new technique that could hasten the development of new drugs for today’s ...

Minimal changes alter an enzyme dramatically

Jan 19, 2010

A new study by a research team at Uppsala University shows how new functions can develop in an enzyme. This can explain, for example, how resistance to toxins can occur so simply. The findings are now being published in the ...

Recommended for you

Chemical biologists find new halogenation enzyme

Sep 15, 2014

Molecules containing carbon-halogen bonds are produced naturally across all kingdoms of life and constitute a large family of natural products with a broad range of biological activities. The presence of halogen substituents ...

Protein secrets of Ebola virus

Sep 15, 2014

The current Ebola virus outbreak in West Africa, which has claimed more than 2000 lives, has highlighted the need for a deeper understanding of the molecular biology of the virus that could be critical in ...

Protein courtship revealed through chemist's lens

Sep 15, 2014

Staying clear of diseases requires that the proteins in our cells cooperate with one another. But, it has been a well-guarded secret how tens of thousands of different proteins find the correct dancing partners ...

Decoding 'sweet codes' that determine protein fates

Sep 15, 2014

We often experience difficulties in identifying the accurate shape of dynamic and fluctuating objects. This is especially the case in the nanoscale world of biomolecules. The research group lead by Professor Koichi Kato of ...

User comments : 0